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Review
. 2022 Nov;188(11):3343-3349.
doi: 10.1002/ajmg.a.62954. Epub 2022 Aug 16.

First report of a short in-frame biallelic deletion removing part of the EGF-like domain calcium-binding motif in LTBP4 and causing autosomal recessive cutis laxa type 1C

Jean-Marie Ravel  1   2 , Margot Comel  1 , Marion Wandzel  1 , Myriam Bronner  1 , Aurélie Tatopoulos  3 , Mathilde Renaud  2   4 , Laëtitia Lambert  2   4 , Anne-Claire Bursztejn  5 , Céline Bonnet  1   2
Affiliations
Review

First report of a short in-frame biallelic deletion removing part of the EGF-like domain calcium-binding motif in LTBP4 and causing autosomal recessive cutis laxa type 1C

Jean-Marie Ravel et al. Am J Med Genet A. 2022 Nov.

Abstract

Cutis laxa (CL) is a rare connective tissue disorder characterized by wrinkled, abundant and sagging skin, sometimes associated with systemic impairment. Biallelic alterations in latent transforming growth factor beta-binding protein 4 gene (LTBP4) cause autosomal recessive type 1C cutis laxa (ARCL1C, MIM #613177). The present report describes the case of a 17-months-old girl with cutis laxa together with a literature review of previous ARCL1C cases. Based on proband main clinical signs (cutis laxa and pulmonary emphysema), clinical exome sequencing (CES) was performed and showed a new nine base-pairs homozygous in-frame deletion in LTBP4 gene. RT-PCR and cDNA Sanger sequencing were performed in order to clarify its impact on RNA. This report demonstrates that a genetic alteration in the EGF-like 14 domain calcium-binding motif of LTBP4 gene is likely responsible for cutis laxa in our patient.

Keywords: LTBP4; Urban-Rifkin-Davis syndrome (URDS); autosomal recessive cutis laxa type 1C (ARCL1C); calcium-binding epidermal growth factor-like domain.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
(a) Pedigree. Clinical features (b) loose and flabby skin (c) aged and wrinkled appearance, hypertelorism, periorbital swelling, long philtrum, depressed nasal bridge, microretrognathia, rather large ears, and prominent cheeks due to sagging skin (d) thoracic CT‐scan showing pulmonary emphysema, ventilatory anomalies and a bronchogenic cyst and (e) thoracic X‐ray showing emphysema
FIGURE 2
FIGURE 2
Molecular analysis. (a) Next‐generation sequencing screenshot from IGV showing homozygous deletion of nucleotides “GACAATGAC.” (b) Equivalent deletions (the resulting sequence is the same because of GA motif repetition). (c) Electropherograms from cDNA sequencing showing “CGTCATTGT” nucleotides deletion on reverse strand and leading to the three amino‐acids deletion. The red arrow head indicates the deleted bases localization. (d) BlastP species conservation showing strong conservation of the deleted pattern across vertebrates
See this image and copyright information in PMC

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Supplementary concepts